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Acetic Acid → 6-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine

HRID 2381082
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HRID 2381082 반응식
CCN(C(C)C)C(C)C.[N:10]1([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH2:33][CH2:34][C:35]5[N:36]([C:38]([C:41]([F:44])([F:43])[F:42])=[N:39][N:40]=5)[N:37]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[C:45](O)(=[O:47])[CH3:46].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:45]([N:13]1[CH2:12][CH2:11][N:10]([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([CH:26]3[CH2:27][CH2:28][N:29]([C:32]4[CH2:33][CH2:34][C:35]5[N:36]([C:38]([C:41]([F:44])([F:43])[F:42])=[N:39][N:40]=5)[N:37]=4)[CH2:30][CH2:31]3)=[CH:24][CH:25]=2)[CH2:15][CH2:14]1)(=[O:47])[CH3:46]
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참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685023596-[4-[4-[3-(Piperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine

생성물 1

HCID 46893584
6-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine
수율 46.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

DIPEA (0.159 mL, 0.92 mmol) was added to 6-[4-[4-[3-(piperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine (150 mg, 0.31 mmol), acetic acid (0.021 mL, 0.37 mmol) and HATU (139 mg, 0.37 mmol) in DMF (2 mL). The resulting solution was stirred at ambient temperature for 16 hours then purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to give 6-[4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (75 mg, 46.1%) as a solid.

후처리

  1. customthen purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  2. additionFractions containing the desired compound
  3. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-c94fba69af384e21b1ea604693bc557f
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08258140B2

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